The broad objective of the proposed research is to establish a binding model and solution complex structure for the interaction of anthracycline drugs (e.g., adriamycin and daunorubicin) with deoxyribonucleic acids (DNA). The process will first involve determining a quantative binding model for the anthracycline-DNA complex using the neighbor exclusion model with corrections for steric and electrostatic interactions among bound drug molecules. Using this model the position of the anthracycline aminosugar substituent in the complex will be determined using glucocylated T4 DNA. The base pair binding specificity will be determined both from the binding model and from equilibrium dialysis in three chamber cells with DNA samples of different A:T/G:C composition. Very low molecular weight DNA will also be prepared by sonication and fractionation for use in determining the length increase when the anthracyclines bind to DNA (viscometric titration) and also to allow NMR measurements on the complex. Low molecular weight DNA is necessary for viscometric measurements to remain near the persistence length for the polymer and is necessary for NMR investigations to obtain a low enough correlation time to get adequate signal to noise. Closed circular superhelical plasmid DNA will be prepared and used for determining unwinding angles for the double helix on intercalation of anthracycylines. All of these experiments together will allow a detailed model to developed for the anthracycline-DNA complex which should help elucidate the mode of antineoplastic action of these drugs and which should suggest modifications to the basic anthracycline which could enhance their medicinal activity. These investigations should also help determine optimum conditions for administration of anthracycline-DNA complexes as therapeutic agents.